Effect of heparin on the production of matrix metalloproteinases and tissue inhibitors of metalloproteinases by human dermal fibroblasts |
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Authors: | Gogly B Dridi M Hornebeck W Bonnefoix M Godeau G Pellat B |
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Institution: | Laboratory of Physiopathology of Non-Mineralized Tissues, University René Descartes Paris V, U.F.R. Odontology, 1 rue M. Arnoux, Montrouge, 92120, France. |
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Abstract: | The influence of heparin and a heparin fragment devoid of anticoagulant activity on the production of matrix metalloproteinases and tissue inhibitors of metalloproteinases by human dermal fibroblasts was studied. Doses (0.1-400 microg/ml) responses were performed and data obtained were similar whatever heparin or fragment was used. The basal expression of collagenase by fibroblasts decreased quasi-linearly with increasing doses of heparins from 1 to 400 microg/ml. TIMP-1 levels were not affected by supplementing serum free culture medium with heparins. On the contrary, at low concentration, i.e. 1-10 microg/ml, heparins stimulated the secretion of both 72-kDa gelatinase (1.4-1.6-fold) and particularly TIMP-2 (>4-fold). At high doses, MMP-2 and TIMP-2 production by fibroblasts returned to basal levels. These results suggested that the local concentration of heparin released by mast cells could be instrumental in modulating fibroblast growth and proteolytic phenotype. |
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Keywords: | heparin fibroblasts skin matrix metalloproteinases tissue inhibitor of metalloproteinases |
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